This study is a 5-year, randomized, double-blind clinical trial designed to evaluate the effectiveness of low dosage levels of isotretinoin in reducing the incidence of basal cell carcinoma in a high-risk population, and to examine possible side effects associated with long-term administration of low doses of isotretinoin. A total of 981 subjects were entered over 36 months at 8 participating clinical centers located around the country. At each center, subjects were randomly allocated to intervention (10 mg/day) or control (placebo) groups. Active intervention concluded in June 1990. The rationale for this study includes the following. Laboratory experiments have shown that retinoids administered to animals can prevent chemical carcinogenesis. In the experimental animals, retinoids were effective even if administered after exposure to the carcinogen, and therefore the prophylactic effect of the retinoids is believed to be in the postinitiation phase, i.e., during the promotion phase of carcinogenesis. Recent case reports have shown that isotretinoin can prevent the appearance of new basal cell carcinoma for 4 years in patients at higher risk of developing new tumors.